In vitro short-term bactericidal activity and accumulation of NM394, the active metabolite of prulifloxacin,for Staphylococcus aureus,Escherichia coli and Pseudomonas aeruginosa: comparison with ciprofloxacin,levofloxacin, and gatifloxacin

The in vitro short-term bactericidal activity and accumulation of NM394, the active metabolite of prulifloxacin, was compared with those of ciprofloxacin (CPFX), levofloxacin (LVFX) and gatifloxacin (GFLX), using Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Of the 4 fluoroquinolones examined, NM394 accumulated to the highest concentration in all three strains. The order of concentration of the fluoroquinolones accumurated in S. aureus 209P JC-1, E. coli NIHJ JC-2 and P. aeruginosa PAO1 were NM394 > CPFX > GFLX > or = LVFX. The accumulation of fluoroquinolones into bacterial cells correlated with their MICs of the drugs for E. coli and P. aeruginosa, whereas there was no correlation between the accumulation and MICs of the drugs for S. aureus. We also studied the reduction of viable cells after addition of each fluoroquinolones to clarify relationship between the short-term bactericidal activity and the accumulation of the quinolones. The short-term bactericidal activity of NM394 against S. aureus 209P JC-1, E. coli NIHJ JC-2 and P. aeruginosa PAO1 were stronger than those of CPFX, LVFX and GFLX when compared at the same concentration. In conclusion, the strong short-term bactericidal activity of NM394 may be attributed to its high accumulation in bacterial cells.     

Inhibitory activity of NM394, the active form of prodrug prulifloxacin against type II topoisomerase from Pseudomonas aeruginosa

The inhibitory activity of NM394, the active form of the prodrug prulifloxacin, against type II topoisomerase from Pseudomonas aeruginosa was compared with those of ciprofloxacin (CPFX), levofloxacin (LVFX) and gatifloxacin (GFLX). The 50% inhibitory concentrations (IC50S) of NM394 for supercoiling activity of DNA gyrase and the decatenation activity of topoisomerase IV were 1.21 and 21.1 micrograms/ml, respectively. The IC50 of NM394 was equal to that of CPFX and lower than those of LVFX and GFLX. The inhibitory activity of the four drugs for DNA gyrase was also corresponding to the antimicrobial activity of the drugs for P. aeruginosa PAO1. The IC50S of the drugs tested for the decatenation activity of topoisomerase IV were from 17.4 to 24.2 times higher than those for the supercoiling activities of DNA gyrase. These results show that DNA gyrase is more sensitive to quinolones than is topoisomerase IV and may be a primary target of quinolones in P. aeruginosa. We concluded that NM394 exerts the potent antimicrobial activity through its strong inhibitory activity for DNA gyrase.     

In vitro activities of levofloxacin and other antibiotics against fresh clinical isolates

In this study, the in vitro activity of levofloxacin (LVFX) against 1,020 fresh bacterial clinical isolates was compared with the activities of a range of ofloxacin, ciprofloxacin (CPFX), ampicillin (ABPC), cefaclor, cefpodoxime, methicillin and benzylpenicillin. The clinical isolates except Vibrio cholerae were collected in Japan during 1998 from patients with infectious diseases. MICs were determined using the agar dilution method according to the recommendations by the Japan Society of Chemotherapy. Some isolates of methicillin resistant Staphylococcus aureus (MRSA) and coagulase negative Staphylococcus were resistant to fluoroquinolones, but the MIC50 of LVFX against MRSA was 6.25 micrograms/ml. LVFX was the most active against MRSA among the antibiotics tested. Most of Staphylococcus epidermidis strains were susceptible to the fluoroquinolones. LVFX showed greater activity against all streptococci strains compared with fluoroquinolones tested. In particular, all Streptococcus pneumoniae strains including PRSP were susceptible to LVFX at < or = 1.56 micrograms/ml. Among Enterococcus, ABPC showed superior activity against Enterococcus faecalis but many isolates of Enterococcus species were resistant to ABPC. LVFX was more active against to these Enterococcus species compared with other fluoroquinolones. On the other hand, LVFX and CPFX showed similar activity against isolates of Enterobacteriaceae. CPFX had an MIC50/90 of 0.20, 0.39 microgram/ml and LVFX showed an MIC50/90 of 0.78, 1.56 micrograms/ml against Pseudomonas aeruginosa. LVFX (MIC50/90 0.10, 0.20 microgram/ml) was more active against Acinetobacter species than CPFX (MIC50/90 0.10, 0.39 microgram/ml). Haemophilus influenzae, Branhamella (Moraxella) catarrhalis and V. cholerae were inhibited by low concentration of the fluoroquinolones tested. The MIC90 of LVFX and CPFX were < or = 0.10 microgram/ml against above three species. Some isolates of Neisseria gonorrhoeae and Campylobacter species were moderately resistant to the fluoroquinolones tested but the MIC50 of LVFX and CPFX were < or = 0.39 microgram/ml. Among anaerobes, Propionibacterium acnes was more susceptible than Peptostreptococcus species, and the MIC90 of beta-lactams and fluoroquinolones tested were < or = 0.78 microgram/ml. In conclusion, this study, performed on large number of strains, confirmed an excellent and wide spectrum antibacterial activity of LVFX compared with the fluoroquinolones and beta-lactams tested. And our results suggest that LVFX may be useful in the treatment of various bacterial infections.     

In vitro antibacterial activity of prulifloxacin, a new oral quinolone, and comparative susceptibility rate at clinical breakpoint MIC

In vitro drug sensitivity of clinically isolated bacteria against prulifloxacin (PUFX), which is a new quinolone, was investigated, and the antibacterial activity and susceptibility rate at clinical breakpoint were compared with those of norfloxacin, ofloxacin (OFLX), ciprofloxacin, tosufloxacin, fleroxacin, sparfloxacin and levofloxacin (LVFX). The following results were obtained. 1) PUFX showed a broad-spectrum antibacterial activity against both Gram-positive and Gram-negative bacteria. 2) MIC80 of PUFX was 0.25 and 1 microgram/ml, against methicillin susceptible Staphylococcus aureus and Streptococcus pneumoniae, respectively and below 0.125 microgram/ml against Gram-negative Enterobacteriaceae. MIC90 of PUFX against Pseudomonas aeruginosa, which has MIC not exceeding 4 micrograms/ml to OFLX, was 0.5 microgram/ml. 3) PUFX was judged as active against the bacteria under the criteria proposed presented by "the Sensitivity Determination Committee for Antibiotics, Japan Society of Chemotherapy: Break Point for Respiratory Infectious Diseases and Sepsis". It is suggested that the sensitivity of each bacterial species to PUFX was high. 4) From the correlation analysis of MIC, PUFX was shown to have two to eight times higher antibacterial acitivity than LVFX for Citrobacter freundii, Serratia marcescens and Pseudomonas aeruginosa. 5) PUFX showed potent short-time bactericidal activity against S. aureus and P. aeruginosa.     

The frequency of Streptococcus pneumoniae strains and sensitivity surveillance for several antibiotics in Gifu Prefecture

The frequency and the antibacterial sensitivity of Streptococcus pneumoniae strains isolated from 6 key hospitals (in 5 areas) and 1 otorhinolaryngology clinic in Gifu Prefecture from February to March, 1999, were investigated with several antibiotics. A total of 128 strains of Streptococcus pneumoniae were isolated throughout the study: 47 strains (36.7%) of penicillin-susceptible S. pneumoniae (PSSP), 51 strains (39.8%) of penicillin-intermediate S. pneumoniae (PISP), and 30 strains (23.4%) of penicillin-resistant S. pneumoniae (PRSP); the resistant bacteria being relatively prominent. In these hospitals, PSSP was isolated by 38.8% in all the key hospitals and by 30% in the otolaryngology clinic with almost no discernible difference. PISP was isolated by 63.3%, higher in the otolaryngology clinic and PRSP by 28.6%, higher in the key hospitals conversely. The MIC90s in PISP and PRSP were determined with the antibiotics. In result, only cefditoren (CDTR) showed favorable antibacterial activities with the MIC90 of 0.78 microgram/ml among penicillins or oral cephems. The MIC90s of carbapenems such as imipenem (IPM), meropenem (MEPM), and panipenem (PAPM) were less than 0.39 microgram/ml; particularly, PAPM showed the highest antibacterial activities. Among new quinolones such as tosufloxacin (TFLX), levofloxacin (LVFX), sparfloxacin (SPFX), and ciprofloxacin (CPFX), TFLX showed the highest antibacterial activities with the MIC90 of 0.39 microgram/ml. Other agents showed very low antibacterial activities as the MIC90s were 25 micrograms/ml in minocycline (MINO) and more than 100 micrograms/ml in clarithromycin (CAM) and clindamycin (CLDM).     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from patients with urinary tract infections (1997). I. Susceptibility distribution

The frequencies of isolation and susceptibilities to antimicrobial agents were investigated on 560 bacterial strains isolated from patients with urinary tract infections (UTIs) in 9 hospitals during the period of June 1997 to May 1998. Of the above bacterial isolates, Gram-positive bacteria accounted for 29.3% and a majority of them were Enterococcus faecalis. Gram-negative bacteria accounted for 70.7% and most of them were Escherichia coli. Susceptibilities of several isolated bacteria to antimicrobial agents were as followed; 1. Enterococcus faecalis Ampicillin (ABPC) showed the highest activity against E. faecalis isolated from patients with UTIs. Its MIC90 was 1 microgram/ml. Imipenem (IPM) and vancomycin (VCM) were also active with the MIC90s of 2 micrograms/ml. The others had low activities with the MIC90s of 16 micrograms/ml or above. 2. Staphylococcus aureus including MRSA VCM and arbekacin (ABK) showed the highest activities against both S. aureus and MRSA isolated from patients with UTIs. The MIC90s of them were 1 microgram/ml. The others except minocycline (MINO) had low activities with the MIC90s of 32 micrograms/ml or above. More than a half of S. aureus strains (including MRSA) showed high susceptibilities to gentamicin (GM) and MINO, the MIC50s of 0.25 microgram/ml or 0.5 microgram/ml. 3. Enterobacter cloacae IPM showed the highest activity against E. cloacae. The MICs for all strains were equal to or lower than 1 microgram/ml. The MIC90s of ciprofloxacin (CPFX) and tosufloxacin (TFLX) were 1 microgram/ml, the MIC90s of amikacin (AMK) and ofloxacin (OFLX) were 4 micrograms/ml, the MIC90 of GM was 16 micrograms/ml. Among E. cloacae strains, those with low susceptibilities to quinolones have decreased in 1997, compared with those in 1996. But the other drugs were not so active in 1997 as 1996. 4. Escherichia coli All drugs except penicillins were active against E. coli with the MIC90s of 8 micrograms/ml or below. Particularly, flomoxef (FMOX), cefmenoxime (CMX), cefpirome (CPR), cefozopran (CZOP), IPM, CPFX and TFLX showed the highest activities against E. coli with the MIC90s of 0.125 microgram/ml or below. 5. Klebsiella pneumoniae K. pneumoniae was susceptible to almost all the drugs except penicillins. Carumonam (CRMN) had the strongest activity with the MICs for all strains equal to or lower than 0.125 microgram/ml. FMOX, CPR, CZOP, CPFX and TFLX were also active with the MIC90s of 0.125 microgram/ml or below. The MIC90s of quinolones had changed into a better state in 1997, compared with those in 1996. 6. Proteus mirabilis Almost all the drugs except ABPC and MINO showed high activities against P. mirabilis. CMX, ceftazidime (CAZ), latamoxef (LMOX), CPR, cefixime (CFIX), cefpodoxime (CPDX) and CRMN showed the highest activities against P. mirabilis. The MICs of them for all strains were equal to or lower than 0.125 microgram/ml. CPFX and TFLX were also active with the MIC90s of 0.125 microgram/ml or below. 7. Pseudomonas aeruginosa The MIC90 of GM was 8 micrograms/ml, the MIC90s of AMK, IPM and meropenem (MEPM) were 16 micrograms/ml. The others were not so active against P. aeruginosa with the MIC90s of 32 micrograms/ml or above. The MIC90s of quinolones had changed into a lower state in 1997, compared with those in 1996. 8. Serratia marcescens IPM showed the highest activity against S. marcescens. Its MIC90 was 2 micrograms/ml. GM was also active with the MIC90 of 4 micrograms/ml. The MIC90s of the others were 16 micrograms/ml or above. The MIC50s of CRMN was 0.125 microgram/ml or below, the MIC50s of CPR and CZOP were 0.25 microgram/ml.     

Alteration of antibacterial activity of tosufloxacin and various antibacterial agents against Streptococcus pneumoniae

The minimum inhibitory concentrations (MICs) of tosufloxacin (TFLX), levofloxacin (LVFX), ciprofloxacin (CPFX), gatifloxacin (GFLX), sparfloxacin (SPFX), azithromycin (AZM), cefteram (CFTM), cefdinir (CFDN) and cefpodoxime (CPDX) against 337 clinical isolates of Streptococcus pneumoniae isolated from Japanese hospital from 1997 to 2002 were investigated by agar plate method. The incidence of penicillin-susceptible S. pneumoniae (PSSP), penicillin-intermediate resistant S. pneumoniae (PISP), and penicillin-resistant S. pneumoniae (PRSP) in each year was studied, and the MICs of antibacterial agents against these strains were determined. As the results, the total incidence of PSSP, PISP, and PRSP was 51.0%, 40.4% and 8.6%, respectively. The incidences of PSSP from 1997 to 2002 were 46.0-55.9%, and were almost definite in each year. In quinolone antibiotics, the differences of antibacterial activity among TFLX, SPFX, and GFLX against PSSP, PISP, and PRSP, were not observed, and these 3 quinolones had potent antibacterial activity. Although CPFX and LVFX showed antibacterial activity as well as other quinolones by 2001, the CPFX-resistant or LVFX-intermediate resistant strains of PSSP were seen with 56.5% and 91.3% in 2002, respectively. Thirty percents of each PSSP, PISP, and PRSP strains were AZM-resistant strains. Such tendency of increase was recognized in PSSP. Against cephem antibiotics, the incidence of intermediate resistant and resistant strains was higher for PISP and PRSP than for PSSP. No difference in the incidence of resistant strains was noted among CFTM, CFDN, and CPDX.     

Antibacterial activity of gatifloxacin against various fresh clinical isolates in 2002

Antibacterial activities of gatifloxacin (GFLX) and other antibacterial drugs against various fresh clinical strains (800 isolates) isolated from specimens of patients in 2002 were compared. GFLX was more active than levofloxacin and ciprofloxacin against Gram-positive bacteria such as methicillin susceptible Staphylococcus aureus and Streptococcus pneumoniae. For these isolates, clarithromycin and azithromycin were less active (MIC90; > 16- > 64 micrograms/mL), GFLX was more active than cefdinir. For Escherichia coli, Klebsiella pneumoniae, Acinetobacter species, Haemophilus influenzae and Moraxella (Branhamella) catarrhalis, three quinolones including GFLX were potently active (MIC90; < or = 0.06-0.5 microgram/mL). Pseudomonas aeruginosa isolated from urinary tract infections were resistant to three quinolones including GFLX (MIC90; 32-64 micrograms/mL), however P. aeruginosa isolated from respiratory and otolaryngological infections were more susceptible (MIC90; 0.5-2 micrograms/mL). Quinolones were less active against Neisseria gonorrhoeae as compared with the cephem antibiotics tested, but GFLX was the most active against N. gonorrhoeae among the quinolones tested. In this study, we investigated activity of GFLX against fresh clinical strains isolated early in 2002, GFLX is widely and potently active against S. aureus, S. pneumoniae and various Gram-negative bacteria.     

Nationwide sensitivity surveillance of ciprofloxacin and various parenteral antibiotics against bacteria isolated from patients with severe infections--the first Ciproxan IV special investigation in 2001

The parenteral injection of ciprofloxacin (CPFX), a fluoroquinolone antimicrobial drug, was approved in September 2000 and a re-examination period of 6 years was set at that time. As a special investigation to apply for re-examination of this drug, it has been planned to conduct 3 nationwide surveillances during the re-examination period by collecting clinically isolated bacteria from patients with severe infections, to whom the drug was mainly indicated, and examining drug susceptibilities of the bacteria to various parenteral antimicrobial drugs including CPFX. This time, we determined the minimum inhibitory concentrations (MICs) of various parenteral antimicrobial drugs including CPFX against 1,220 strains isolated from patients with severe infections by the micro-liquid dilution method and compared susceptibilities of various clinically isolated bacteria to CPFX with those to other antimicrobial drugs. Gram-positive bacteria were less susceptible to CPFX than to carbapenems except 2 bacterial species, Enterococcus faecium and Enterococcus avium but susceptibilities of methicillin-susceptible Staphylococcus aureus (MSSA), Staphylococcus epidermidis and Enterococcus faecalis to CPFX were comparable to those to cefozopran. Susceptibility of Streptococcus pneumoniae to CPFX did not differ among ampicillin (ABPC)-susceptible Streptococcus pneumoniae (MIC of ABPC: < 0.25 microgram/ml), ABPC-intermediate S. pneumoniae (MIC of ABPC: 0.25-2 micrograms/ml) and ABPC-resistant S. pneumoniae (MIC of ABPC: > or = 4 micrograms/ml) MIC90 of CPFX: 1 microgram/ml) and a decrease in the antimicrobial activity seen among cephem and carbapenem antimicrobial drugs against penicillin-intermediate strains was not noted with CPFX. Gram-negative bacteria were susceptible to CPFX similarly to carbapenems and the MIC90 values of CPFX were in the range from < or = 0.063 to 2 micrograms/ml against strains except Stenotrophomonas maltophilia and Burkholderia cepacia. Pseudomonas aeruginosa was most susceptible to CPFX among the antibacterial drugs examined and the MIC90 was 2 micrograms/ml. CPFX also showed the lowest MIC90 value (0.5 microgram/ml) against beta-lactam-resistant P. aeruginosa among the drugs examined. When extended-spectrum beta-lactamase (ESBL) production and class B beta-lactamase production were examined in 439 strains of Enterobacteriaceae and 168 strains of glucose non-fermentative bacteria out of the Gram-negative bacteria collected this time, 3 strains (0.49%) producing ESBL and 7 strains (1.15%) producing class B beta-lactamase were found. The MIC range of CPFX to these 10 strains was between < or = 0.063 to 8 micrograms/ml and 5 strains among those showed susceptibilities (MIC of CPFX: 1 microgram/ml) based on the NCCLS breakpoint. CPFX also showed a satisfactory result concerning susceptibilities of major causal bacteria based on the report of the committee of Japan Society of Chemotherapy on the standard method for determination of susceptibility to antimicrobial agents, the breakpoint of pneumonia. Furthermore, susceptibilities of various bacteria isolated clinically from patients with severe infections this time did not differ much from the result of the nationwide surveillance which we conducted in 1997. Thus, it was concluded that the antimicrobial activity of CPFX was maintained in the post-marketing surveillance for its parenteral preparation.     

Antibacterial activity of fosfomycin against the causative bacteria isolated from bacterial enteritis

The in vitro antibacterial activities of fosfomycin (FOM) and 3 fluoroquinolones against Salmonella spp., pathogenic Escherichia coli, Campylobacter spp. and Shigella spp. were investigated. The activity upon the environmental condition in the inflammation was compared with standard condition in vitro. On standard condition, the MIC90 of tosfloxacin (TFLX), norfloxacin (NFLX) and levofloxacin (LVFX) against E. coli (77 strains), Shigella spp. (50) and Salmonella spp. (41) were < or = 0.025-0.10, 0.10, and 0.05 microgram/ml, respectively. The MIC90 of FOM against those organisms was 0.39-1.56 micrograms/ml. The MIC90 of TFLX, NFLX, LVFX against Campylobacter spp. were 6.25, 100 and 3.13 micrograms/ml, respectively. The MIC90 of FOM was 50 micrograms/ml. The activity of FOM was unaffected by pH and in anaerobic condition. On the other hand, the activity of NFLX was decreased in low pH and in anaerobic condition. In the presence of horse blood and addition of Na+, the activities of both agents were unaffected. These results suggested that FOM is equally active with or superior to fluoroquinolone in the intestinal infection treatment.     

Nationwide sensitivity surveillance of various antibiotic activities against bacteria isolated from patients with severe infections]

The susceptibility of 3,058 bacterial strains isolated between January and March, 1997 from patients with severe infections in Japan to ciprofloxacin and other injectable antimicrobial agents was measured using broth microdilution method. Methicillin-resistant Staphylococcus aureus (MRSA) strains were generally sensitive to vancomycin, teicoplanin and arbekacin, and resistant to CPFX and other antibacterial agents. MIC90 of CPFX against Streptococcus pneumoniae, to which MIC of ampicillin was more than 4 micrograms/mL, was below 2 micrograms/mL. PRSP (Penicillin resistant S. pneumoniae), which was also resistant to cephalosporins and carbapenems, showed no cross-resistance to CPFX. The susceptibility of Gram-negative bacteria to CPFX was as high as that to carbapenems. Especially, MIC90 against Pseudomonas aeruginosa was 2 micrograms/mL. 3 strains of isolated 446 P. aeruginosa strains had blaIMP gene. CPFX and pazufloxacin demonstrated good susceptibility with 0.25 microgram/mL of MIC to 2 strains of these 3 strains. The susceptibility rate of the most common isolates from patients suffering from lower respiratory tract infections excluding MRSA to CPFX was more than 80% (indication: % strains < pneumonia break point).     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1988). I. Susceptibility distribution]

Isolation frequencies and sensitivities to antibacterial and antibiotic agents were investigated on 801 bacterial strains isolated from patients with urinary tract infections in 9 hospitals during the period of June to November 1988. Of the above total bacterial population, Gram-positive bacteria accounted for 29.3% and a majority of them were Enterococcus spp. Gram-negative bacteria accounted for 70.7% and most of them were Escherichia coli. 1. Enterococcus faecalis: Vancomycin was most active with its MIC90 < or = 0.78 microgram/ml. Ampicillin, piperacillin, ofloxacin (OFLX), ciprofloxacin (CPFX) and imipenem (IPM) were also active. 2. Staphylococcus aureus: Arbekacin and minocycline were most active with their MIC90s 0.39 microgram/ml and 1.56 micrograms/ml, respectively. Among penicillins, dicloxacillin was the most active. Activities of cephems were considerably lower. 3. E. coli: Most of the agents were tested active. Particularly the second and third generation cephems were active in a range of < or = 0.10-0.20 microgram/ml. Carumonam (CRMN), IPM, OFLX and CPFX were also active with MIC90s < or = 0.10 microgram/ml. 4. Klebsiella pneumoniae CRMN and IPM were highly active. Penicillins generally showed lower activities. Cephems and new quinolones had high activities with their MIC90s in a range of 0.39-0.78 microgram/ml. 5. Proteus mirabilis: The third generation cephems were active with their MIC90s in a range of < or = 0.10-0.20 microgram/ml. CRMN, OFLX and CPFX were also active with their MIC90s < or = 0.10 microgram/ml, 0.39 microgram/ml and 0.20 microgram/ml, respectively. 6. Pseudomonas aeruginosa: IPM and tobramycin were active with their MIC90s 1.56 micrograms/ml and 3.13 micrograms/ml, respectively. CRMN and new quinolones showed MIC80s of 25-100 micrograms/ml. Most of penicillins and cephems were not active. 7. Other Gram-negative rods: Against Citrobacter freundii, Enterobacter cloacae and Serratia marcescens, IPM, CPFX and OFLX were active. Penicillins and cephems were not so active. CRMN was active against S. marcescens with its MIC80 at 6.25 micrograms/ml.     

司帕沙星和妥舒沙星的体内外抗菌作用研究

目的观察国产司帕沙星、妥舒沙星及其它四种氟喹诺酮类抗菌药对成都地区780株临床分离菌的体外抗菌活性，并比较司帕沙星、妥舒沙星和环丙沙星对金葡球菌、大肠埃希菌和铜绿假单胞菌感染小鼠的体内抗菌活性。方法用琼脂稀释法测定国产司帕沙星和妥舒沙星的MIC50和MIC90，并与其它四种氟喹诺酮类抗菌药进行了比较。本文还测定了抗菌药对金葡球菌、大肠埃希菌和铜绿假单胞菌感染小鼠治疗的ED50结果体外试验表明司帕沙星和妥舒沙星能有效抑制或杀灭革兰阳性、革兰阴性菌及厌氧菌，显示了广谱抗菌活性。司帕沙星和妥舒沙星对革兰阳性菌的抗菌活性是环丙沙星的2～8倍，氧氟沙星和氟罗沙星的4～16倍，是诺氟沙星的16～32倍。司帕沙星对MRSA的抗菌活性与妥舒沙星相似，但优于环丙沙星、氧氟沙星、氟罗沙星和诺氟沙星。司帕沙星对大多数革兰阴性菌的抗菌活性与环丙沙星和妥舒沙星相似，是氧氟沙星、氟罗沙星和诺氟沙星的2～8倍。两药对厌氧菌的抗菌活性也较环丙沙星强。口服或皮下注射司帕沙星对金葡球菌和大肠埃希菌所致小鼠全身性感染的保护作用优于环丙沙星和妥舒沙星。同一给药途径下司帕沙星对铜绿假单胞菌所致小鼠全身性感染的保护作用与妥舒沙星和环丙沙星相似。三种受试药对金葡球菌和大肠埃希菌所致小鼠全身性感染的保护作用优于铜绿假单胞菌所致感染。结论司帕沙星和妥舒沙星对革兰阳性菌和厌氧菌的体外抗菌活性优于环丙沙星和其它药物，对大多数革兰阴性菌的抗菌活性与环丙沙星相似，但优于其它受试药。司帕沙星对金葡球菌和大肠埃希菌所致小鼠全身性感染的体内保护作用优于环丙沙星和妥舒沙星。同一给药途径下司帕沙星对铜绿假单胞菌所致小鼠全身性感染的保护作用与妥舒沙星和环丙沙星相似。     

In vitro antibacterial activity of various cephems against clinical isolates from complicated urinary tract infections

In vitro antibacterial activity of several cephems (CEZ as the first generation (group A); CTM and CMZ as the second generation (group B); CMX, CPZ, LMOX, CTX and CZX as the third generation (group C)) against 8 species, each of 54 strains, of Gram-negative clinical isolates from complicated urinary tract infection was compared by determination of the MICs. The following results were obtained: The most sensitive drugs against each species in MIC80; CTX (MIC80 0.20 microgram/ml) against E. coli, CMX (1.56 microgram/ml) against K. pneumoniae, LMOX (0.39 microgram/ml) against P. mirabilis, LMOX (0.78 microgram/ml) against Indole (+) Proteus, CMX and CPZ (50 micrograms/ml) against E. cloacae, CMX and LMOX (50 micrograms/ml) against C. freundii, CMX (3.13 micrograms/ml) against S. marcescens and CPZ (25 micrograms/ml) against P. aeruginosa The most sensitive drugs against each species in MICS100; CMX (MIC100 3.13 micrograms/ml) against E. coli, CMX (6.25 micrograms/ml) against K. pneumoniae, CTX (0.78 microgram/ml) against P. mirabilis, LMOX (1.56 microgram/ml) against Indole (+) Proteus, CPZ (100 micrograms/ml) against E. cloacae, CMX (100 micrograms/ml) against C. freundii, CMX (12.5 microgram/ml) against S. marcescens and CPZ (50 micrograms/ml) against P. aeruginosa. In each species, the group C were most sensitive followed by those of the group B. Many isolates were highly resistant to the group A (especially in C. freundii, S. marcescens and P. aeruginosa).     

Susceptibility of clinical isolates to aztreonam

In vitro antibacterial activities of 9 antibiotics including aztreonam (AZT) against clinically isolated Gram-negative bacteria were determined using MIC-2000 plus system. Bacteria were isolated from clinical materials in Saga Medical School during a period from May 1987 to March 1988. Summarized results were as follows: 1. AZT showed excellent antibacterial activities against Escherichia coli, Klebsiella pneumoniae, Proteus sp. and Haemophilus influenzae, and MIC80 values of AZT against these organisms were lower than 0.20 microgram/ml. 2. Antibacterial activities of AZT were superior to cephem antibiotics compared against Enterobacter aerogenes, Enterobacter cloacae, Citrobacter freundii and Serratia marcescens. 3. The MIC50 and MIC80 of AZT against Pseudomonas aeruginosa were 12.5 micrograms/ml and 25 micrograms/ml, respectively. 4. AZT did not show any antibacterial activity against Acinetobacter sp. and Xanthomonas maltophilia.     

Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibiotics (2000)

From October 2000 to September 2001, we collected the specimen from 410 patients with lower respiratory tract infections in 16 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various anti-bacterial agents and antibiotics and patients' characteristics. Of 499 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in inflammation, 493 strains were investigated. The breakdown of the isolated bacteria were: Staphylococcus aureus 78, Streptococcus pneumoniae 73, Haemophilus infiuenzae 99, Pseudomonas aeruginosa (non-mucoid) 64, P. aeruginosa (mucoid) 14, Klebsiella pneumoniae 25, Moraxella subgenus Branhamella catarrhalis 21, etc. Of 78 S. aureus strains, those with 4 micrograms/ml or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) occupied 53.8%. Vancomycin and arbekacin had the most potent activities against MRSA as observed in 1999. The frequency of S. pneumoniae exhibiting low sensitivity to penicillin (penicillin-intermediate S. pneumoniae: PISP + penicillin-resistant S. pneumoniae: PRSP) was 38.4% being consistent with that in 1999 (34.7%). PRSP accounted for 11.0% of the total, being more than that in 1999 (3.0%). Carbapenems had strong activities against S. pneumoniae. Especially, panipenem inhibited the growth of all 73 strains at 0.125 microgram/ml. Generally, all drugs had strong activities against H. influenzae with MIC80s of 8 micrograms/ml or less. The drug that had the strongest activity against H. infiuenzae was levofloxacin, which inhibited the growth of 94 of the 99 strains at 0.063 microgram/ml. Tobramycin had a strong activity against P. aeruginosa (both mucoid and non-mucoid) with MIC80 of 1 microgram/ml. The mucoid strain was little isolated (14 strains) but the susceptibilities to all drugs were better than the non-mucoid strain. K. pneumoniae showed good susceptibilities to all drugs except ampicillin and the MIC80S were 2 micrograms/ml or less. Particularly, cefpirome, cefozopran, and levofloxacin had strong bactericidal activities against K. pneumoniae with MIC80s of 0.125 microgram/ml, and cefotiam, second-generation cephems, also had a favorable activity being MIC80 of 0.25 microgram/ml. Also, all drugs generally had strong activities against M. (B.) catarrhalis. MIC80s of all drugs were 2 micrograms/ml or less. The drug having the strongest activity was imipenem and levofloxacin inhibiting all 21 strains at 0.063 microgram/ml. Most of the patients with respiratory infection were aged 70 years or older, accounting for approximately a half of the total (44.4%). As for the incidence by the diseases, bacterial pneumonia and chronic bronchitis were the highest, being noted in 38.0% and 31.7% of all the patients, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (18.3%) and S. pneumoniae (16.1%). In contrast, H. infiuenzae (20.4%) and P. aeruginosa (both mucoid and non-mucoid: 16.7%) were frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from all the patients were S. pneumoniae (24.3%) and H. infiuenzae (26.7%). The frequency of isolated S. pneumoniae tended to decrease with the increase in the number of administration days while that of isolated H. infiuenzae did not. The frequency of isolated P. aeruginosa tended to increase with the duration of administration. The isolated bacteria were comparable between the patients already treated with penicillins and cephems. In the patients treated with aminoglycosides, macrolides, and quinolones, P. aeruginosa was most frequently isolated (33.3 to 40.0%).     

Comparative studies on activities of antimicrobial agents against causative organisms isolated from urinary tract infections (1986). I. Susceptibility distribution

Susceptibilities to various antibacterial and antibiotic agents of bacterial strains isolated from urinary tract infections at 8 hospitals in Japan from July to October in 1986 are summarized as follows. 1. Enterococcus faecalis was susceptible to sulfamethoxazole/trimethoprim (ST) and imipenem (IPM) with MIC90s of 0.78 and 1.56 microgram/ml. Minocycline had the strongest activity against Staphylococcus aureus; the MICs for all strains tested were lower than 0.39 microgram/ml. The MIC80s of dicloxacillin, and arbekacin (HBK) were 0.20 and 0.78 microgram/ml, respectively. Among the cephems, the MIC80 of flomoxef was 25 micrograms/ml, whereas those of cefmenoxime (CMX) and cefotiam (CTM) were 50 micrograms/ml. 2. Escherichia coli was most susceptible to ofloxacin (OFLX) among the oral antibacterial and antibiotic agents tested. OFLX showed the minimum inhibitory concentration against 90% (MIC90) of the 274 strains of E. coli tested to be lower than 0.10 microgram/ml. The antibacterial activities of the third generation cephems such as CMX and latamoxef (LMOX) were the strongest among the injectable antibiotics tested. The MIC90s of CMX and LMOX were lower than 0.10 and 0.20 microgram/ml, respectively. CTM and cefmetazole, the second generation cephems, were also highly active against E. coli with MIC90s of 0.39 and 1.56 micrograms/ml, respectively. 3. Among the oral antibacterial and antibiotic agents tested, OFLX was the most active against Klebsiella pneumoniae. Its MIC90 was 0.78 microgram/ml. Among the injectable antibiotics tested, CMX was the strongest with an MIC90 of 0.20 microgram/ml; MIC90 of CTM and LMOX were 0.39 microgram/ml. 4. The tested antibacterial and antibiotic agents were generally less active against Citrobacter freundii than against other bacteria. The MIC80 of OFLX was 0.39 microgram/ml. Gentamicin (GM) and ST were slightly active against C. freundii. Among the cephems, CMX had the MIC80 of 25 micrograms/ml. 5. Enterobacter cloacae was less susceptible to the cephems tested. OFLX, GM, and mecillinam were active against this bacteria with MIC80s of 0.78, 0.78 and 1.56 micrograms/ml, respectively. 6. Among the oral antibacterial and antibiotic agents and penicillins examined, piperacillin (PIPC) was the most active against Proteus mirabilis. Its MIC90 was 0.39 microgram/ml. Those of sulbenicillin, cefaclor, ampicillin, OFLX, and ST were 0.78, 0.78, 1.56, 3.13 and 3.13 micrograms/ml, respectively. CMX was highly active against P. mirabilis with an MIC90 of less than or equal to 0.10 microgram/ml; LMOX followed with an MIC90 of 0.20 microgram/ml among the injectable antibiotics tested. CTM was also active against this bacterium; the MIC90 was 0.39 microgram/ml. 7. The antibacterial and antibiotic agents were generally only slightly active against Proteus vulgaris.(ABSTRACT TRUNCATED AT 400 WORDS)     

Evaluation of antibiotics by the method of initial bactericidal activity

Minimum inhibitory concentration (MIC) has been generally used to evaluate the activity of antimicrobial agents. However, there is some discrepancy between clinical efficacy and the MIC value. We studied the relationship between initial bactericidal activity of imipenem (IPM), panipenem (PAPM), meropenem (MEPM), ceftazidime (CAZ) and amikacin (AMK) and the respective MIC values against Pseudomonas aeruginosa PAO1. Initial bactericidal activity was defined as percent reduction of initial bacterial cell concentration (10(6) cells/ml) after 1 hour incubation following addition of antibiotic. The concentration of antibiotic used in this experiment was the blood level of each antibiotic at 3 hours after administration by drip infusion of the usual dose (IPM, PAPM and CAZ were 1 g for 1 hour drip infusion, MEPM was 1 g for 0.5 hours drip infusion and AMK was 200 mg for 1 hour drip infusion, respectively). The antibiotic concentration of IPM, PAPM, MEPM, CAZ and AMK were 8.77 micrograms/ml, 6.37 micrograms/ml, 4.12 micrograms/ml, 12.0 micrograms/ml and 5.18 micrograms/ml, respectively. MICs of IPM, PAPM, MEPM, CAZ and AMK were 2 micrograms/ml, 64 micrograms/ml, 1 microgram/ml, 1 microgram/ml and 2 micrograms/ml, respectively. Initial bactericidal activity of IPM, PAPM, MEPM, and CAZ against P. aeruginosa PAO1 was 98.2%, 86.1%, 48.1%, and 43.4% reduction in bacterial concentration, respectively. AMK shows the strongest initial bactericidal activity with more than 99.9%. The killing speed of IPM was obviously the most rapid among the three carbapenems. The MIC of PAPM was significantly higher than the other antibiotics, and the initial bactericidal activity of PAPM was second to IPM. We can classify antibiotics into two groups based on initial bactericidal activity against P. aeruginosa; one class is antibiotics having rapid initial killing such as AMK, IPM and PAPM, the other is CAZ, MEPM showing slow initial killing.     

Levofloxacin in the field of dermatology]

1. Minimum inhibitory concentrations (MICs) of levofloxacin (LVFX, DR-3355), ofloxacin (OFLX), tosufloxacin (TFLX), norfloxacin (NFLX) were determined, with an inoculum size of 10(6) cfu/ml, against 122 strains of Staphylococcus aureus isolated from lesions of skin infections. LVFX showed most frequent MIC values of 0.20 micrograms/ml. OFLX, TFLX, and NFLX showed most frequent MIC values of 0.39 micrograms/ml, less than or equal to 0.05 micrograms/ml and 0.78 micrograms/ml, respectively. 2. Serum and skin levels of LVFX after oral administration (10 mg/kg, fasting) were determined in rats. Serum levels were 1.79, 1.29, 0.60, 0.43 and 0.18 micrograms/ml, and corresponding skin levels were 1.63, 1.77, 1.04, 0.87 and 0.64 micrograms/g (wet weight) at 0.5, 1, 2, 4 and 8 hours after administration (n = 5), respectively. 3. LVFX was used clinically in 43 cases at doses of 200-300 mg divided into 2 or 3 doses, and evaluated for final overall clinical efficacy in 41 cases. Cure was observed in 21 cases, remarkable improvement in 13 cases, improvement in 4 cases, unchanged in 1 case, aggravation in 1 case, and remarkable aggravation in 1 case. Diarrhea was observed in 2 cases, diffuse erythema with feverishness in 1 case and slight dyspnea in 1 case. Transient slight eosinophilia, elevation of Al-P, anemia and leukopenia were observed.     

In vitro antibacterial activity and beta-lactamase stability of cefodizime, a new cephalosporin antibiotic

The in vitro activity and beta-lactamase stability of cefodizime (HR 221), a new cephalosporin, were compared with those of other cephem antibiotics. HR 221 was highly active against Gram-negative bacteria. The compound inhibited growth of all tested Haemophilus influenzae strains at 0.10 microgram/ml and showed strong activity even against penicillin-resistant Neisseria gonorrhoeae strains, but it was less effective against Pseudomonas aeruginosa than the other antibiotics tested. Against Gram-positive bacteria, HR 221 showed 100% inhibition of growth of Streptococcus pneumoniae at 0.39 microgram/ml, and it was slightly less active against Staphylococcus aureus (MIC90:12.5 micrograms/ml) than other antibiotics such as cefotaxime (CTX). The bactericidal activity of HR 221 against E. coli was dose-related and comparable to that of CTX, cefoperazone and latamoxef. The bactericidal activity of the compound at medium concentrations simulating human serum levels was higher than that of CTX and cefmetazole, and no cell regrowth was noted after beta-lactamase-induced inactivation of the compound. HR 221 was stable to most drug-inactivating enzyme preparations from various bacterial species.